Schulz R, Gres P, Heusch G
Abteilung für Pathophysiologie, Zentrum Innere Medizin, Universitätsklinikum Essen, 45122 Essen, Germany.
Am J Physiol Heart Circ Physiol. 2001 May;280(5):H2175-81. doi: 10.1152/ajpheart.2001.280.5.H2175.
Endogenous opioids are involved in ischemic preconditioning (IP) in several species. Whether or not opioids are important for IP and short-term myocardial hibernation (STMH) in pigs is currently unknown. In 34 enflurane-anesthetized pigs, the left anterior descending coronary artery was flow constantly perfused. Subendocardial blood flow (Endo), infarct size (IS; percent area at risk), and the free energy change of ATP hydrolysis (DeltaG) were determined. After 90-min severe ischemia and 120-min reperfusion, IS averaged 28.3 +/- 5.4% (means +/- SE) (n = 8; Endo: 0.047 +/- 0.009 ml. min(-1) x g(-1)). IP by 10-min ischemia and 15-min reperfusion reduced IS to 9.9 +/- 3.8% (P < 0.05, n = 8; Endo: 0.044 +/- 0.009 ml. min(-1) x g(-1)). After naloxone (1 mg/kg iv followed by 2 microg x kg(-1) x min(-1)), IS averaged 25.8 +/- 7.0% (n = 6; Endo: 0.039 +/- 0.008 ml x min(-1) x g(-1)) without and 24.7 +/- 4.7% (n = 6; Endo: 0.044 +/- 0.006 ml x min(-1) x g(-1)) with IP. At 5-min moderate ischemia in the presence of naloxone, Endo decreased from 0.90 +/- 0.07 to 0.28 +/- 0.03 ml x min(-1) x g(-1)and DeltaG decreased from -58.6 +/- 1.0 to -52.6 +/- 0.4 kJ/mol. Prolongation of ischemia to 90 min did not alter Endo, but DeltaG recovered toward control values (57.7 +/- 1.1 kJ/mol), and the myocardium remained viable. These responses are identical to those of nonnaloxone-treated pigs. Endogenous opioids are involved in IP but not in STMH in pigs.
内源性阿片肽在多个物种的缺血预处理(IP)中发挥作用。目前尚不清楚阿片肽对猪的IP和短期心肌冬眠(STMH)是否重要。在34只接受恩氟烷麻醉的猪中,对左前降支冠状动脉进行持续血流灌注。测定心内膜下血流量(Endo)、梗死面积(IS;危险区域面积百分比)以及ATP水解的自由能变化(ΔG)。在经历90分钟严重缺血和120分钟再灌注后,IS平均为28.3±5.4%(均值±标准误)(n = 8;Endo:0.047±0.009 ml·min⁻¹·g⁻¹)。通过10分钟缺血和15分钟再灌注进行IP,可将IS降至9.9±3.8%(P < 0.05,n = 8;Endo:0.044±0.009 ml·min⁻¹·g⁻¹)。给予纳洛酮(静脉注射1 mg/kg,随后以2 μg·kg⁻¹·min⁻¹)后,未进行IP时IS平均为25.8±7.0%(n = 6;Endo:0.039±0.008 ml·min⁻¹·g⁻¹),进行IP时IS平均为24.7±4.7%(n = 6;Endo:0.044±0.006 ml·min⁻¹·g⁻¹)。在纳洛酮存在的情况下,5分钟中度缺血时,Endo从0.90±0.07降至0.28±0.03 ml·min⁻¹·g⁻¹,ΔG从 -58.6±1.0降至 -52.6±0.4 kJ/mol。将缺血延长至90分钟并未改变Endo,但ΔG恢复至对照值(57.7±1.1 kJ/mol),心肌仍保持存活。这些反应与未用纳洛酮处理的猪相同。内源性阿片肽参与猪的IP,但不参与STMH。